Our laboratory has been studying alterations in MMTV proviral gene expression during mammary gland tumorigenesis in a "clean" inbred mouse strain (C3H/Sm). This strain is of interest because there is "normal" expression of MMTV RNA transcripts in their mammary glands but no viral proteins or virions are produced. We have previously shown that the abundance of these endogenous MMTV transcripts is increased both in mammary tumors induced by chemicals and/or pituitary isografts and in spontaneous mammary tumors from old untreated multiparous C3H/Sm females. By far the most abundant MMTV trancript in these neoplasms was an anomalous 2.2 Kb RNA containing MMTV LTR sequences exclusively. This observation has been extended to include mammary preneoplasias in C3H/Sm mice (hyperplastic alveolar outgrowths) which were induced by hormonal or chemical treatment in virgin female mice. We have demonstrated that these preneoplastic lesions anachronistically possess enhanced activities of their casein and Alpha-lactalbumin genes in the absence of hormone stimulation or pregnancy. Further study has demonstrated that these preneoplastic mammary lesions release humoral factors which profoundly effect the growth and development of normal mammary tissue in the distal mammary fat pads of their host. The relationship between these altered gene regulatory processes following transformation and the increased expression of MMTV LTR RNA expression is under study.